It is known to provide radiopharmaceutical compositions in sealed containers which are fitted with pharmaceutical grade closures, thus permitting the withdrawal of one or more doses for patient administration from the container.
A huge variety of pharmaceutical grade closures are commercially available, in a wide range of materials, shapes and sizes, together with optional coatings comprising a range of materials [Hencken & Petersen, Pharm. Ind., 65(9a), 966-976 (2003)]. The selection of a particular class or type of closure with the optimum characteristics for a given type of product is therefore not straightforward.
U.S. Pat. No. 6,162,648 provides a method of purification of the radioisotope 111In for radiopharmaceutical use. U.S. Pat. No. 6,162,648 teaches (Column 2) that, when a closure-sealed vial is used for the 111In, a rubber stopper coated with PTFE (polytetrafluoroethylene) on the surfaces facing the solution is beneficial. The coating is said to prevent leaching of impurities from the rubber of the stopper into the radioactive solution. Preferred stoppers of U.S. Pat. No. 6,162,648 are made of vinyl butyl rubber with the coating preferably the Teflon™ brand of PTFE.
WO 2006/026603 discloses improved containers for radioisotope generators, especially radiopharmaceutical generators for the positron-emitting radioisotope 82Rb. An improved crimped-on stopper seal is described, which is made of a material resistant to or tolerant of radiation and which can withstand pressure without ballooning. A range of coated and uncoated stopper materials was studied for suitability, especially with respect to resistance to radiation doses comparable to those prevailing during the working lifetime of the generator. Three uncoated elastomeric stopper materials were identified as preferred: 4588/40 isoprene/chlorobutyl; 6720 bromobutyl and 140/0 chlorobutyl. The most preferred stopper material was said to be 4588/40 isoprene/chlorobutyl.
Dalkyo Seiko's technical information sheet on their Fluorotec™-coated stoppers (D21 Formulation), where Fluorotec™ is Dalkyo's brand of ETFE, lists various advantages for the laminated fluoro resin film closure:                (i) an effective barrier to drug-closure interaction, preventing deterioration of the drug product and thus enhancing stability, maintaining potency and extending shelf-life. Applicable for drugs packaged at very low or very high pH;        (ii) eliminates endogenous particles of rubber stoppers;        (iii) excellent resistance to drug-closure adsorption, thus compatible with low dose and low volume fill drugs;        (iv) laminated coating provides excellent lubricity, eliminating closure sticking or clumping problems during batch manufacture and eliminating the need for silicone treatments of the closure.        
The Dalkyo Seiko catalogue suggests that the closures are useful for freeze-dried preparations, powdered preparations, liquid preparations and transfusion preparations. The Catalogue states that the closures should not be exposed to direct sunlight or intense ultraviolet rays, and are supplied non-sterile (ie. for pharmaceutical applications must be sterilised before use). Both the technical information sheet and Catalogue are silent on radiopharmaceutical applications and/or whether the closures are radioresistant (ie. can withstand radiation dose).